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Susceptibility to flavivirus-specific antiviral response of Oas1b affects the neurovirulence of the Far-Eastern subtype of tick-borne encephalitis virus

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Abstract

Tick-borne encephalitis virus (TBEV) is a zoonotic agent that causes fatal encephalitis in humans. 2’-5’-oligoadenylate synthetase 1b (Oas1b) has been identified as a flavivirus resistance gene, but most inbred laboratory mice do not possess a functional Oas1b gene. In this study, a congenic strain carrying a functional Oas1b gene, B6.MSM-Oas, was used to evaluate the pathogenicity of Far-Eastern TBEV. Although intracerebral infection of B6.MSM-Oas mice by Oshima 5-10 resulted in limited signs of illness, infection by Sofjin-HO resulted in death with severe neurologic signs. While Oshima 5-10 was cleared from the brain, Sofjin-HO was not cleared despite a similar level of expression of the intact Oas1b gene. Necrotic neurons with viral antigens and inflammatory reactions were observed in the brain infected with Sofjin-HO. These data indicate that the different susceptibility to the antiviral activity of Oas1b resulted in a difference in neurovirulence in the two TBEV strains.

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Abbreviations

BHK:

Baby hamster kidney

B6:

C57BL/6J

CNS:

Central nervous system

FCS:

Fetal calf serum

LD50 :

50 % lethal dose

MEM:

Minimum essential medium

OAS:

2’-5’-oligoadenylate synthetase

Oas1b:

2’-5’-oligoadenylate synthetase 1b

pfu:

Plaque-forming unit

TBE:

Tick-borne encephalitis

TBEV:

Tick-borne encephalitis virus

TBST:

TBS containing 0.01% Tween 20

WNV:

West Nile virus

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Acknowledgments

This work was supported by Grants-in-Aid for Scientific Research (22780268) and the Global COE Program from the Ministry of Education, Culture, Sports, Sciences and Technology of Japan, and Health Sciences Grants for Research on Emerging and Re-emerging Infectious Disease from the Ministry of Health, Labour and Welfare of Japan.

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Correspondence to Kentaro Yoshii.

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Yoshii, K., Moritoh, K., Nagata, N. et al. Susceptibility to flavivirus-specific antiviral response of Oas1b affects the neurovirulence of the Far-Eastern subtype of tick-borne encephalitis virus. Arch Virol 158, 1039–1046 (2013). https://doi.org/10.1007/s00705-012-1579-1

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  • DOI: https://doi.org/10.1007/s00705-012-1579-1

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